Development of new physical gels based on chitosan for wound healing.

Purpose: Chitosan (CHI) is a hydrophilic polymers largely investigated for biomedical applications due to its biocompatibility, biodegradability, cheapness. Moreover, antimicrobic properties and induction of cell proliferation have been attributed to this natural polymer. Here, we proposed new formulations based on a CHI, alone or associated to actives, for application on wound healing. Methods: CHI was autoclaved and the resulting powder was dissolved at 2% w/w in acetic acid 0.1 M; the dispersion was sonicated for 30-40 min and then placed in an oven at 37 ° C under vacuum for 48h. CHI gels were differently loaded depending of the considered active. In particular, gels loaded with PDGF and FGF-?? were prepared by co-dissolution of the growth factors with CHI in acetic acid 0.1 M. Alternatively, Centella asiatica (CEN) or Echinacea angustifolia (ECH) were added to the preformed gel. Thermal and rheological analysis were carried out to highlight the differences due to the heat treatment and the viscoelastic properties of gels. In addition, the effects of the gels on human fetal foreskin fibroblasts (HFFF-2) viability, proliferation and migration were investigated. Results: The differential scanning calorimeter (DSC) analysis showed that, the thermal treatment modifies the chemical and physical characteristics of the CHI. Furthermore, the formulations with non-autoclaved CHI showed a rheological behavior typical of an entangled viscous solution, while gels prepared from the autoclaved CHI have a typical gel behavior. The loading of actives into the gel did not affect the rheological properties of the formulations which remained those of a typical gel. In vitro tests on HFFF-2 showed that CHI gels were not toxic and led to increased cell proliferation and migration. Finally, the presence of PDGF ,FGF-??, CEN or ECH in the gels shows to enhance the migration, the proliferation without affecting the vitality of fibroblasts. Conclusions: The gels developed in this work could be proposed as new product for the medication of would, i.e. pressure ulcers. In vivo experiments are in progress to clarify the advantage of this new medication and to understand what active, among that used in this work, are actually interesting to load into the gels.